Terns Pharmaceuticals’ decision to drop its liver disease ambitions may yet pay off, after the biotech posted phase 1 data showing one of its other candidates induced 5% weight loss in a month.
The small-scale, 28-day study saw 36 healthy adults with obesity or overweight receive one of three oral doses of the GLP-1 agonist, dubbed TERN-601, or placebo. The nine individuals who received the highest, 740 mg, dose of TERN-601 saw a placebo-adjusted mean weight loss of 4.9%, while those who received the 500 mg and 240 mg doses saw weight loss of 3.8% and 1.9%, respectively.
At the top dose, 67% of participants lost 5% or more of their baseline body weight, the biotech explained in a Sept. 9 release.
The drug was well tolerated with no treatment-related dose interruptions, reductions or discontinuations at any dose, Terns said. Over 95% of treatment-emergent adverse effects (AEs) were mild.
At the highest dose, six of the nine patients experienced grade 2—moderate—AEs and none suffered grade 3 or above, according to the data.
“All gastrointestinal events were mild to moderate and consistent with the GLP-1R agonist class,” the company said. “Importantly, there were no clinically meaningful changes in liver enzymes, vital signs or electrocardiograms observed.”
Mizhuo analysts said they were “very pleased with the totality of the data,” noting in particular “no red flags.” The company’s stock was trading up 15% at $9 in pre-market trading on Monday morning compared to a Friday closing price of $7.81.
Terns is late to an obesity space dominated by Novo Nordisk and Eli Lilly’s injectable GLP-1 drugs WeGovy and Zepbound, respectively. Novo’s drug in particular is marketed on the back of average weight loss of almost 15% over the far longer time frame of 68 weeks.
Today’s short-term data of Terns’ oral drug bears more similarity to Viking Therapeutics, which showed in March that 57% of the seven patients who received 40 mg doses of its oral dual GLP-1 and GIP receptor agonist saw their body weight fall by 5% or more.
Terns said that TERN-601 has “distinct properties that may be advantageous for an oral GLP-1R agonist,” citing the drug’s “low solubility and high gut permeability.” These attributes may allow for longer absorption of the drug into the gut wall, which could trigger the part of the brain that controls hunger.
“Additionally, TERN-601 has a low free fraction in circulation which, combined with the flat PK curve, may be allowing TERN-601 to be well tolerated when administered at high doses,” the company added.
Terns is looking to “swiftly advance” TERN-601 into a phase 2 trial next year, and has hopes to showcase TERN-601’s potential as both a monotherapy for obesity as well as in combination with other candidates from its pipeline—namely the thyroid hormone receptor-beta agonist TERN-501 or a GIPR modulator from its TERN-800 program.
The biotech halted work on developing the phase 2-stage TERN-501 in metabolic dysfunction-associated steatohepatitis (MASH) at the start of this year after the company found little interest from potential partners in pushing forward in the tricky liver indication. That decision led the company to pivot its attention to TERN-601 for obesity as well as TERN-701 in chronic myeloid leukemia.